Oxytocin-Augmented Modular-Based Group Intervention for Loneliness: A Proof-Of-Concept Randomized Controlled Trial.

INTRODUCTION: Loneliness poses a significant health problem and existing psychological interventions have shown only limited positive effects on loneliness. Based on preliminary evidence for impaired oxytocin signaling in trait-like loneliness, the current proof-of-concept study used a randomized, double-blind, placebo-controlled design to probe intranasal oxytocin (OT) as an adjunct to a short-term modular-based group intervention for individuals suffering from high trait-like loneliness (HL, UCLA Loneliness Scale ≥55). METHODS: Seventy-eight healthy HL adults (56 women) received five weekly group psychotherapy sessions. HL participants received OT or placebo before the intervention sessions. Primary outcomes were trait-like loneliness measured at baseline, after the intervention, and again at two follow-up time points (3 weeks and 3 months), and, assessed at each session, state loneliness (visual analog scale), perceived stress (Perceived Stress Scale, PSS-10), quality of life (World Health Organization Five Well-Being Index, WHO-5), and the therapeutic relationship (Group Questionnaire, GQ-D). RESULTS: The psychological intervention was associated with significantly reduced perceived stress and improved trait-like loneliness across treatment groups, which was still evident at the 3-month follow-up. OT had no significant effect on trait-like loneliness, quality of life, or perceived stress. However, compared to placebo, OT significantly facilitated the decrease in state loneliness within sessions and significantly improved positive bonding between the group members. CONCLUSION: Despite significantly improved trait-like loneliness after the intervention, OT did not significantly augment this effect. Further studies are needed to determine optimal intervention designs to translate the observed acute effects of OT into long-term benefits.

Creative mindset reduces racial ingroup bias in empathic neural responses.

Spontaneous racial categorization of other-race individuals provides a cognitive basis of racial ingroup biases in empathy and prosocial behavior. In two experiments, we investigated whether fostering a creativity mindset reduces racial ingroup biases in empathy and undermines spontaneous racial categorization of other-race faces. Before and after a creative mindset priming procedure that required the construction of novel objects using discreteness, we recorded electroencephalography signals to Asian and White faces with painful or neutral expressions from Chinese adults to assess neural activities underlying racial ingroup biases in empathy and spontaneous racial categorization of faces. We found that a frontal-central positive activity within 200 ms after face onset (P2) showed greater amplitudes to painful (vs. neutral) expressions of Asian compared with White faces and exhibited repetition suppression in response to White faces. These effects, however, were significantly reduced by creative mindset priming. Moreover, the creative mindset priming enhanced the P2 amplitudes to others' pain to a larger degree in participants who created more novel objects. The priming effects were not observed in control participants who copied objects constructed by others. Our findings suggest that creative mindsets may reduce racial ingroup biases in empathic neural responses by undermining spontaneous racial categorization of faces.

Behavioral and Neural Dissociation of Social Anxiety and Loneliness.

Loneliness is a public health concern with detrimental effects on physical and mental well-being. Given phenotypical overlaps between loneliness and social anxiety (SA), cognitive-behavioral interventions targeting SA might be adopted to reduce loneliness. However, whether SA and loneliness share the same underlying neurocognitive mechanisms is still an elusive question. The current study aimed at investigating to what extent known behavioral and neural correlates of social avoidance in SA are evident in loneliness. We used a prestratified approach involving 42 (21 females) participants with high loneliness (HL) and 40 (20 females) participants with low loneliness (LL) scores. During fMRI, participants completed a social gambling task to measure the subjective value of engaging in social situations and responses to social feedback. Univariate and multivariate analyses of behavioral and neural data replicated known task effects. However, although HL participants showed increased SA, loneliness was associated with a response pattern clearly distinct from SA. Specifically, contrary to expectations based on SA differences, Bayesian analyses revealed moderate evidence for equal subjective values of engaging in social situations and comparable amygdala responses to social decision-making and striatal responses to positive social feedback in both groups. Moreover, while explorative analyses revealed reduced pleasantness ratings, increased striatal activity, and decreased striatal-hippocampal connectivity in response to negative computer feedback in HL participants, these effects were diminished for negative social feedback. Our findings suggest that, unlike SA, loneliness is not associated with withdrawal from social interactions. Thus, established interventions for SA should be adjusted when targeting loneliness.SIGNIFICANCE STATEMENT Loneliness can cause serious health problems. Adapting well-established cognitive-behavioral therapies targeting social anxiety might be promising to reduce chronic loneliness given a close link between both constructs. However, a better understanding of behavioral and neurobiological factors associated with loneliness is needed to identify which specific mechanisms of social anxiety are shared by lonely individuals. We found that lonely individuals show a consistently distinct pattern of behavioral and neural responsiveness to social decision-making and social feedback compared with previous findings for social anxiety. Our results indicate that loneliness is associated with a biased emotional reactivity to negative events rather than social avoidance. Our findings thus emphasize the distinctiveness of loneliness from social anxiety and the need for adjusted psychotherapeutic protocols.

Differential contribution of between and within-brain coupling to movement synchronization.

A fundamental characteristic of the human brain that supports behavior is its capacity to create connections between brain regions. A promising approach holds that during social behavior, brain regions not only create connections with other brain regions within a brain, but also coordinate their activity with other brain regions of an interaction partner. Here we ask whether between-brain and within-brain coupling contribute differentially to movement synchronization. We focused on coupling between the inferior frontal gyrus (IFG), a brain region associated with the observation-execution system, and the dorsomedial prefrontal cortex (dmPFC), a region associated with error-monitoring and prediction. Participants, randomly divided into dyads, were simultaneously scanned with functional near infra-red spectroscopy (fNIRS) while performing an open-ended 3D hand movement task consisting of three conditions: back-to-back movement, free movement, or intentional synchronization. Results show that behavioral synchrony was higher in the intentional synchrony compared with the back-to-back and free movement conditions. Between-brain coupling in the IFG and dmPFC was evident in the free movement and intentional synchrony conditions but not in the back-to-back condition. Importantly, between-brain coupling was found to positively predict intentional synchrony, while within-brain coupling was found to predict synchronization during free movement. These results indicate that during intentional synchronization, brain organization changes such that between-brain networks, but not within-brain connections, contribute to successful communication, pointing to shift from a within-brain feedback loop to a two-brains feedback loop.

The default network is causally linked to creative thinking.

Creative thinking represents a major evolutionary mechanism that greatly contributed to the rapid advancement of the human species. The ability to produce novel and useful ideas, or original thinking, is thought to correlate well with unexpected, synchronous activation of several large-scale, dispersed cortical networks, such as the default network (DN). Despite a vast amount of correlative evidence, a causal link between default network and creativity has yet to be demonstrated. Surgeries for resection of brain tumors that lie in proximity to speech related areas are performed while the patient is awake to map the exposed cortical surface for language functions. Such operations provide a unique opportunity to explore human behavior while disrupting a focal cortical area via focal electrical stimulation. We used a novel paradigm of individualized direct cortical stimulation to examine the association between creative thinking and the DN. Preoperative resting-state fMRI was used to map the DN in individual patients. A cortical area identified as a DN node (study) or outside the DN (controls) was stimulated while the participants performed an alternate-uses-task (AUT). This task measures divergent thinking through the number and originality of different uses provided for an everyday object. Baseline AUT performance in the operating room was positively correlated with DN integrity. Direct cortical stimulation at the DN node resulted in decreased ability to produce alternate uses, but not in the originality of uses produced. Stimulation in areas that when used as network seed regions produced a network similar to the canonical DN was associated with reduction of creative fluency. Stimulation of areas that did not produce a default-like network (controls) did not alter creative thinking. This is the first study to causally link the DN and creative thinking.

Altered activation in the action observation system during synchronization in high loneliness individuals.

Lonely people tend to evaluate social exchanges negatively and to display difficulties in interactions. Interpersonal synchronization is crucial for achieving positive interactions, promoting affinity, closeness, and satisfaction. However, little is known about lonely individuals' ability to synchronize and about their brain activity while synchronizing. Following the screening of 303 participants, we recruited 32 low and 32 high loneliness participants. They were scanned while engaged in movement synchronization, using a novel dyadic interaction paradigm. Results showed that high loneliness individuals exhibited a reduced ability to adapt their movement to their partner's movement. Intriguingly, during movement adaptation periods, high loneliness individuals showed increased activation in the action observation (AO) system, specifically in the inferior frontal gyrus and the inferior parietal lobule. They did not show increased activation in the dorsomedial prefrontal cortex, which in the context of synchronization was suggested to be related to gap-monitoring. Based on these findings, we propose a model according to which lonely people may require stronger activation of their AO system for alignment, to compensate for some deficiency in their synchronization ability. Despite this hyperactivation, they still suffer from reduced synchronization capacity. Consequently, synchronization may be a relevant intervention area for the amelioration of loneliness.

Biological marker of withdrawal ruptures: Dyadic pattern of incongruence in oxytocin release.

Despite widespread clinical, theoretical, and empirical support for the importance of alliance ruptures, little is known about the underlying biological level at times of rupture. The overarching goal of the present study was to investigate dyadic patterns of in-session oxytocin (OT) change between patients and therapists (e.g., patient's OT increases more than therapist's OT) as markers of withdrawal ruptures. Hypothesis 1 construed that OT incongruence (e.g., larger patient increase in OT in comparison to their therapist OT increase) will mark the occurrence of withdrawal ruptures. Hypothesis 2 construed that this effect of OT incongruence will be more pronounced when anxious attachment orientation is low. Surface analysis was conducted on 628 saliva samples that were gathered before and after therapeutic sessions of 53 patient-therapist dyads enrolled in a randomized control trial treating major depression. Only Hypothesis 2 received empirical support, meaning it was only when anxious attachment orientation was low that there were significantly more withdrawal ruptures when the patient's OT increase was higher than their therapist's OT increase. This is consistent with the literature, suggesting that in times of withdrawal ruptures, the patient and therapist are in an incongruent state. Findings suggest that this incongruence is mirrored at the biological level only when anxious attachment orientation is low. Results shed light on what may be happening between patients and therapists on a biological level during a withdrawal rupture. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Brain-to-brain coupling during handholding is associated with pain reduction.

The mechanisms underlying analgesia related to social touch are not clear. While recent research highlights the role of the empathy of the observer to pain relief in the target, the contribution of social interaction to analgesia is unknown. The current study examines brain-to-brain coupling during pain with interpersonal touch and tests the involvement of interbrain synchrony in pain alleviation. Romantic partners were assigned the roles of target (pain receiver) and observer (pain observer) under pain-no-pain and touch-no-touch conditions concurrent with EEG recording. Brain-to-brain coupling in alpha-mu band (8-12 Hz) was estimated by a three-step multilevel analysis procedure based on running window circular correlation coefficient and post hoc power of the findings was calculated using simulations. Our findings indicate that hand-holding during pain administration increases brain-to-brain coupling in a network that mainly involves the central regions of the pain target and the right hemisphere of the pain observer. Moreover, brain-to-brain coupling in this network was found to correlate with analgesia magnitude and observer's empathic accuracy. These findings indicate that brain-to-brain coupling may be involved in touch-related analgesia.

Oxytocin increases the social salience of the outgroup in potential threat contexts.

A growing body of literature suggests that OT administration may affect not only prosocial outcomes, but also regulate adversarial responses in the context of intergroup relations. However, recent reports have challenged the view of a fixed role of OT in enhancing ingroup favoritism and outgroup derogation. Studying the potential effects of OT in modulating threat perception in a context characterized by racial miscegenation (Brazil) may thus afford additional clarification on the matter. In a double-blind, placebo-controlled study, White Brazilian participants completed a first-person shooter task to assess their responses towards potential threat from racial ingroup (White) or outgroup (Black) members. OT administration enhanced the social salience of the outgroup, by both increasing the rate at which participants refrained from shooting unarmed Black targets to levels similar to White targets, and by further increasing the rate of correct decisions to shoot armed Black targets (versus White armed targets). In summary, our results indicate that a single dose of OT may promote accurate behavioral responses to potential threat from members of a racial outgroup, thus offering support to the social salience hypothesis.

Oxytocin as a biomarker of the formation of therapeutic alliance in psychotherapy and counseling psychology.

The therapeutic alliance is one of the most consistent predictors of therapeutic change, including symptom reduction and improvement in wellbeing and quality of life, across a variety of mental health interventions. Yet, little is known about its biological mechanisms. Oxytocin (OT) has been suggested as a biological mechanism by which bonds are formed and strengthened across species. This article is intended to demonstrate the potential of OT as a biomarker of therapeutic change in psychotherapy and counseling psychology, especially of the therapeutic alliance. We delineate three main potential paths of investigation based on the most recent research on OT in parent-child and romantic partner dyads. For each path, we provide a detailed explanation for whom, when, and how OT should be measured. Each path is illustrated using data collected in a randomized controlled trial of psychotherapy for major depressive disorder. These illustrations demonstrate the great potential of OT as a biomarker of (a) trait-like characteristics of the patients and the therapists, (b) the processes of therapeutic change, and (c) the dyadic synchrony between patients and their therapists. The potential clinical contribution of OT as a biomarker for each of these three paths is further demonstrated using a case study. Practical suggestions and directions for future research are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Women's Body Odor during Ovulation Improves Social Perception in Single Men.

Previous research has shown that men's mating motivation may increase following exposure to women's body odor during ovulation. In the current study, we examined whether exposure to women's fertility odor cues influences social perception among men, while focusing on the role of men's relationship status in moderating this reaction. We collected body odor samples from 43 women during ovulation and during the luteal phase and exposed 85 men to these odor samples while they performed an emotion recognition task and an interpersonal perception task. Single men were better at recognizing emotional facial expressions following exposure to odor cues of high fertility as compared with odor cues of low fertility. No such effect was identified in pair-bonded men. In support of this finding, single men became more accurate on the interpersonal perception task following exposure to odor cues of high fertility, while pair-bonded men became less accurate after such exposure. Collectively, the results suggest that exposure to women's fertility odor cues improves social perception among single men, while it impairs such perception among pair-bonded men. We suggest that these effects may result from increased mating motivation following exposure to odor cues of fertility, which in turn encourages accurate social perception among single men while promoting an avoidant attitude toward social stimuli among pair-bonded men.

A Time-Varying Measure of Dyadic Synchrony for Three-Dimensional Motion.

We propose a novel approach to the analysis of synchronized three-dimensional motion in dyads. Motion recorded at high time resolution, as with a gaming device, is preprocessed in each of the three spatial dimensions by spline smoothing. Synchrony is then defined, at each time point, as the cosine between the two individuals' estimated velocity vectors. The approach is extended to allow a time lag, allowing for the analysis of leader-follower dynamics. Mean square cosine over the time range is proposed as a scalar summary of dyadic synchrony, and this measure is found to be positively associated with cognitive empathy.

The neural underpinnings of cross-cultural differences in creativity.

Whereas Western individualistic cultures emphasize uniqueness, collectivistic East-Asian cultures discourage it. Here we examined whether cross-cultural differences in creativity as measured by a task of divergent thinking (DT) are explained by enhanced activity in brain regions that mediate inhibitory control (e.g., the left inferior frontal gyrus [L-IFG]). We therefore predicted that the L-IFG would be "hyperactive" among individuals from East-Asian cultures compared to Western ones. In Study 1, Israeli and South Korean participants were compared on a classic DT task (AUT; "Alternate uses: Manual of instructions and interpretation"). Israelis generated more original ideas compared to South Koreans. In Study 2, Israeli participants and South Korean participants currently living in Israel were scanned while performing the AUT. In line with previous studies, the results indicate that generation of original ideas across cultures is associated with activation of the posterior cingulate cortex (PCC), which is part of the default mode network (DMN). As hypothesized, South Koreans showed enhanced activation of the L-IFG compared to Israelis. This enhanced activation was associated with lower originality scores. The cultural dimension of traditionalism, being higher in the South Korean sample than in the Israeli Sample, was related to enhance L-IFG activity, further supporting our hypothesis regarding cultural influences on inhibitory control. Furthermore, functional connectivity analysis indicated that activation of the L-IFG was positively coupled with PCC activity among Israelis and with preSMA activity among South Koreans. The results suggest that cross-cultural differences in creativity might be explained by variations in inhibitory control.

Androstadienone, a Chemosignal Found in Human Sweat, Increases Individualistic Behavior and Decreases Cooperative Responses in Men.

A growing body of evidence suggests that humans can communicate socially relevant information, such as aggression, dominance, and readiness for competition, through chemosensory signals. Androstadienone (androsta-4,16,-dien-3-one), a testosterone-derived compound found in men's axillary sweat, is a main candidate for a human pheromone that may convey such information. The current study aimed to investigate whether androstadienone serves as a chemosignaling threat cue to men, thus triggering avoidance behavior during competitive interaction with another man. In a double-blind, placebo-controlled, within-subject study design, 30 healthy, normosmic, heterosexual male participants completed the social orientation paradigm (SOP), a monetary game played against a fictitious partner that allows 3 types of responses to be measured in the context of provocation: an aggressive response, an individualistic withdrawal response, and a cooperative response. Participants completed the SOP task twice, once under exposure to androstadienone and once under exposure to a control solution. The results indicate that androstadienone increased individualistic responses while it decreased cooperative responses. These findings support the role of androstadienone as a threatening signal of dominance that elicits behavioral avoidance and social withdrawal tendencies, possibly as a submissive response.

The impact of empathy and reappraisal on emotional intensity recognition.

Empathy represents a fundamental ability that allows for the creation and cultivation of social bonds. As part of the empathic process, individuals use their own emotional state to interpret the content and intensity of other people's emotions. Therefore, the current study was designed to test two hypotheses: (1) empathy for the pain of another will result in biased emotional intensity judgment; and (2) changing one's emotion via emotion regulation will modulate these biased judgments. To test these hypotheses, in experiment one we used a modified version of a well-known task that triggers an empathic reaction We found that empathy resulted in biased emotional intensity judgment. To the best of our knowledge, this is the first demonstration of a bias in the recognition of emotional facial expressions as a function of empathy for pain. In experiment two, we replicated these findings in an independent sample, and further found that this biased emotional intensity judgment can be moderated via reappraisal. Taken together, our findings suggest that the novel task used here can be employed to further explore the relation between emotion regulation and empathy.

The role of empathy in the neural responses to observed human social touch.

One of the ways in which individuals convey feelings and thoughts to one another is through touch. Although the neural responses to felt and observed tactile stimuli between an inanimate object and a part of the human body have been vastly explored, the neural responses to observed human interaction involving touch are not well understood. Considering that the observation of social touch involves vicarious sharing of emotions, we hypothesized that levels of empathic traits modulate the neural responses to observed touch and focused on the attenuation in the mu\alpha rhythm (8-13Hz), a neural marker that has been related to sensorimotor resonance. Fifty-four participants observed photos depicting social touch, nonsocial touch, or no touch while their electroencephalography (EEG) activity was recorded. Results showed that interindividual differences in levels of empathic traits modulated both behavioral and electrophysiological responses to human social touch, such that highly empathic participants evaluated human social touch as inducing more pleasant emotions and exhibited greater mu suppression upon observation of human social touch compared to less empathic participants. Specifically, both the behavioral and the electrophysiological responses to observed social touch were predicted by levels of personal distress, a measure of emotional contagion. These findings indicate that the behavioral and electrophysiological responses to observed social touch are modulated by levels of empathy.

Sex dimorphism in a mediatory role of the posterior midcingulate cortex in the association between anxiety and pain sensitivity.

Behavioral studies found greater pain sensitivity in females that vanishes fully or partially when controlling for the emotional state. Furthermore, pain-related brain activation hints at the role of limbic structures in sex differences in pain processing. We aimed to investigate the role of pain-related limbic structures in mediating the relation between subjects' affective state (i.e., anxiety) and pain. Contact heat-evoked potentials (CHEPs) were recorded in 26 healthy subjects (13 males) simultaneously with innocuous (42 °C) baseline and target noxious (52 °C) series of stimuli administered to the left non-dominant volar forearm. The N2 and P2 components were analyzed, and their generators' activity was estimated using standardized low-resolution brain electromagnetic tomography. Thereafter, structural equation modeling (SEM) was applied separately for females and males, examining the mediatory role of the CHEPs' limbic structures generators [posterior midcingulate cortex (pMCC), insula, amygdala, and hippocampus] in the anxiety-pain sensitivity association. Females exhibited greater P2 amplitudes that were highly associated with larger pMCC activity (r = 0.910, p < 0.001). This correlation was also evident in males, though with less strength (r = 0.578, p = 0.039). Moreover, the P2 amplitudes were associated both in females (r = 0.645, p = 0.017) and males (r = 0.608, p = 0.028) with the activity of the amygdala\hippocampus\insula. SEM revealed that the relationship between state anxiety and pain ratings was only in females fully mediated via the effect of the pMCC on the P2 amplitude. These findings suggest that sexual dimorphism in anxiety-related brain activity may explain the differences found in CHEPs and the sex-related association between anxiety and pain.

Generating original ideas: The neural underpinning of originality.

One of the key aspects of creativity is the ability to produce original ideas. Originality is defined in terms of the novelty and rarity of an idea and is measured by the infrequency of the idea compared to other ideas. In the current study we focused on divergent thinking (DT) - the ability to produce many alternate ideas - and assessed the neural pathways associated with originality. Considering that generation of original ideas involves both the ability to generate new associations and the ability to overcome automatic common responses, we hypothesized that originality would be associated with activations in regions related to associative thinking, including areas of the default mode network (DMN) such as medial prefrontal areas, as well as with areas involved in cognitive control and inhibition. Thirty participants were scanned while performing a DT task that required the generation of original uses for common objects. The results indicate that the ability to produce original ideas is mediated by activity in several regions that are part of the DMN including the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC). Furthermore, individuals who are more original exhibited enhanced activation in the ventral anterior cingulate cortex (vACC), which was also positively coupled with activity in the left occipital-temporal area. These results are in line with the dual model of creativity, according to which original ideas are a product of the interaction between a system that generates ideas and a control system that evaluates these ideas.

Dynamic mutual predictions during social learning: A computational and interbrain model.

During social interactions, we constantly learn about the thoughts, feelings, and personality traits of our interaction partners. Learning in social interactions is critical for bond formation and acquiring knowledge. Importantly, this type of learning is typically bi-directional, as both partners learn about each other simultaneously. Here we review the literature on social learning and propose a new computational and neural model characterizing mutual predictions that take place within and between interactions. According to our model, each partner in the interaction attempts to minimize the prediction error of the self and the interaction partner. In most cases, these inferential models become similar over time, thus enabling mutual understanding to develop. At the neural level, this type of social learning may be supported by interbrain plasticity, defined as a change in interbrain coupling over time in neural networks associated with social learning, among them the mentalizing network, the observation-execution system, and the hippocampus. The mutual prediction model constitutes a promising means of providing empirically verifiable accounts of how relationships develop over time.